Hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) MedDRA version: 20.0 Level: PT Classification code 10007509 Term: Cardiac amyloidosis System Organ Class: 10007541 - Cardiac disorders MedDRA version: 20.0 Level: PT Classification code 10019889 Term: Hereditary neuropathic amyloidosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Alnylam Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Male or female age 18 (or age of legal consent, whichever is older) to 85 years of age ? Have a diagnosis of hATTR amyloidosis with documented TTR mutation ? Have a Neuropathy Impairment Score of 5 to 130 (inclusive; this criterion must be met at the Screening Visit 2) ? Have a Polyneuropathy Disability score of =3b (this criterion must be met at the Screening Visit 2) ? Have a Karnofsky Performance Status (KPS) of =60% ?Patient is willing and able to comply with the study requirements and to provide written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 92 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 68
Exclusion criteria
Exclusion criteria: • Has had a liver transplant or is likely, in the opinion of the Investigator, to undergo liver transplantation during the 18-month Treatment Period of the study • Has known other (non-hATTR) forms of amyloidosis or clinical evidence of leptomeningeal amyloidosis • Has a New York Heart Association heart failure classification >2 • Has any of the following laboratory parameter assessments: a. ALT and/or AST >1.5× upper limit of normal reference range (ULN); b. Total bilirubin >ULN (>1.5 ULN in patients with Gilbert's Syndrome) c. INR >1.2 (patients on anticoagulant therapy with an INR of =3.5 will be allowed) • Estimated glomerular filtration rate (eGFR) =30 mL/min/1.73m2 • Has known human immunodeficiency virus (HIV) infection; or evidence of acute or chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection • Has other known causes of sensorimotor or autonomic neuropathy (eg, autoimmune disease, monoclonal gammopathy) that the treating physician believes to be contributing to the neuropathy • Current or future participation in another investigational device or drug study • Is currently taking tafamidis, doxycycline, or tauroursodeoxycholic acid; acid; if previously on any of these agents, must have completed a 14-day wash-out prior to dosing (Day 1) • Is currently taking diflunisal; if previously on this agent, must have at least a 3-day washout prior to dosing (Day 1)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of ALN-TTRSC02 in patients with hATTR amyloidosis by evaluating the effect on neurologic impairment ;Secondary Objective: • To determine the efficacy of ALN-TTRSC02 on quality of life, gait speed, neurologic impairment,nutritional status, and disability •To demonstrate the non-inferiority of ALN-TTRSC02 compared to patisiran with respect to serum TTR levels ;Primary end point(s): • Change from baseline in the Modified Neurologic Impairment Score +7 (mNIS+7) of the ALN-TTRSC02 group compared to the placebo arm of the Phase 3 patisiran-LNP study (ALN-TTR02-004; APOLLO) ;Timepoint(s) of evaluation of this end point: • Change from baseline in the mNIS+7 of the ALN-TTRSC02 group compared to the placebo arm of the APOLLO study at Month 9 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change from baseline in the following parameters of the ALN-TTRSC02 group compared to the placebo arm of the APOLLO (patisiran) study: - Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) total score - Timed 10-meter walk test (10-MWT) - mNIS+7 - Modified body mass index (mBMI) - Rasch-built Overall Disability Scale (R-ODS) • Percent reduction in serum TTR levels in the ALN-TTRSC02 arm compared to the within-study patisiran arm ;Timepoint(s) of evaluation of this end point: • Change from baseline in the following clinical parameters of the ALN-TTRSC02 group compared to the placebo arm of the APOLLO study: - Norfolk Norfolk QoL-DN total score at Month 9 - Timed 10-meter walk test (10-MWT) at Month 9 - mNIS+7 at Month 18 - Norfolk QoL-DN total score at Month 18 - 10-MWT at Month 18 - Modified body mass index (mBMI) at Month 18 - Rasch-built Overall Disability Scale (R-ODS) at Month 18 • Percent reduction in serum TTR levels in the ALN-TTRSC02 arm compared to the within-study patisiran arm through Month 18 | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Cyprus, France, Germany, Greece, Ireland, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, Portugal, Spain, Sweden, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Line
Alnylam Pharmaceuticals, Inc
Outcome results
None listed